OBJECTIVES: To prepare a stable mouse model of chronic liver fibrosis induced by dietary vitamin A (VA) deficiency combined with CCl₄ injections. METHODS: A total of 126 Balb/c mice were randomized into 3 groups for feeding with a normal VA diet or a VA-deficient diet containing 500 or 200 IU/kg VA. After 4 weeks of feeding, half of the mice in each group were given intraperitoneal injections of 5% CCl₄ (10 mL/kg, twice a week) for 8 weeks. Serum retinol, ALT/AST and liver index of the mice were examined, liver tissue pathologies were observed with HE and Masson staining, and liver fibrosis score and oxidative stress level were evaluated. RESULTS: Four weeks of VA-deficient feeding, especially at 200 IU/kg, significantly lowered serum retinol level of the mice. CCl₄ injections for 8 weeks obviously increased liver index and ALT/AST and caused obvious liver fibrosis in all the mice, but liver pathologies were more severe in the 2 VA-deficient groups; severe liver necrosis with inflammatory cell infiltration was observed in 200 IU/kg VA group, where 2 mice died. After discontinuation of CCl₄, the mice with normal dietary VA showed gradual recovery of the liver index, ALT/AST, liver cord structure and liver fibrosis; the mice with VA deficiency, however, showed no significant improvements in these parameters, and the mice with 200 IU/kg VA still had serious abdominal adhesion, false lobules and massive inflammatory cell infiltration with a fibrosis stage score of 3. The oxidative damage index 8-OHdG was significantly higher in 500 IU/kg VA group than in normal VA group after CCl₄ modeling. CONCLUSIONS Feeding with diet containing 500 IU/kg VA for 4 weeks and 10 mL/kg CCl₄ injections for 8 weeks can result in stable moderate to severe liver fibrosis in mice without spontaneous reversal at 8 weeks of drug withdrawal.
Animals ; Mice ; Mice, Inbred BALB C ; Disease Models, Animal ; Carbon Tetrachloride ; Vitamin A Deficiency/complications* ; Male ; Liver Cirrhosis/etiology* ; Oxidative Stress ; Vitamin A/blood*

Objective: To investigate the effects of plasma lipopolysaccharide (LPS) concentration changes on platelet release of vascular endothelial growth factor (VEGF) and thrombospondin (TSP)-1 in patients with decompensated cirrhotic portal hypertension after transjugular intrahepatic portosystemic shunt (TIPS) procedure. Methods: 169 cases with cirrhotic portal hypertension were enrolled, of which 81 cases received TIPS treatment. LPS, VEGF, and TSP-1 concentrations with different Child-Pugh class in peripheral blood plasma of patients were measured. After pre-incubation of normal human platelets with different concentrations of LPS and stimulated by collagen in vitro, platelet PAC-1 expression rate, VEGF, and TSP-1 concentrations were detected. PAC-1 expression rate and the concentrations of LPS, VEGF and TSP-1 in peripheral blood plasma of patients before and after TIPS procedure were detected. The relationship between plasma LPS, VEGF and TSP-1 concentrations and Child-Pugh score changes in patients after TIPS procedure was analyzed. Statistical analysis was performed by t-test, one-way ANOVA or Pearson's rho according to different data. Results: Plasma LPS and TSP-1 concentrations were significantly higher in Child-Pugh class C patients than class A and B, but the concentration of plasma VEGF was significantly lower than class A and B (P < 0.01). In vitro experiments showed that concentration of LPS, TSP-1, and platelet PAC-1 expression rate was higher in the supernatant, but the difference in the concentration of VEGF in the supernatant was not statistically significant. Portal vein pressure and platelet activation were significantly decreased (P < 0.01) in patients after TIPS procedure. Portal venous pressure, platelet activation, plasma LPS, and TSP-1 levels were significantly decreased continuously, while VEGF levels were significantly increased continuously after TIPS procedure. Plasma LPS concentration was positively correlated with TSP-1 concentration (r = 0.506, P < 0.001), and negatively correlated with VEGF concentration (r = -0.167, P = 0.010). Child-Pugh score change range was negatively correlated with change range of plasma VEGF concentration (r = -0.297, P = 0.016), and positively correlated with change range of plasma TSP-1 concentration (r = 0.145, P = 0.031) after TIPS. Conclusion: Portal venous pressure gradient, plasma LPS concentration and corresponding platelet activation was decreased in cirrhotic portal hypertension after TIPS procedure, and with TSP-1 reduction and VEGF elevation it is possible to reduce the liver function injury caused by portal venous shunt.
Blood Platelets ; Humans ; Hypertension, Portal/etiology* ; Lipopolysaccharides ; Liver Cirrhosis/complications* ; Plasma ; Portasystemic Shunt, Transjugular Intrahepatic/adverse effects* ; Vascular Endothelial Growth Factor A

Liver fibrosis is a slow, insidious process involving accumulation of extracellular matrix protein in the liver. The stage of liver fibrosis in chronic liver disease (CLD) determines overall morbidity and mortality; the higher the stage, the worse the prognosis. Noninvasive composite scores can be used to determine whether patients with CLD have significant or advanced fibrosis. Patients with low composite scores can be safely followed up in primary care with periodic reassessment. Those with higher scores should be referred to a specialist. As the epidemic of diabetes mellitus, obesity and non-alcoholic fatty liver diseases is rising, CLD is becoming more prevalent. Easy-to-use fibrosis assessment composite scores can identify patients with minimal or advanced fibrosis, and should be an integral part of decision-making. Patients with cirrhosis, high composite scores, chronic hepatitis B with elevated alanine aminotransferase and aspartate aminotransferase, or deranged liver panel of uncertain aetiology should be referred to a specialist.
Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Decision Making ; End Stage Liver Disease ; complications ; diagnosis ; therapy ; Hepatitis B ; complications ; Humans ; Liver ; pathology ; Liver Cirrhosis ; complications ; diagnosis ; therapy ; Non-alcoholic Fatty Liver Disease ; complications ; diagnosis ; therapy ; Prognosis ; Referral and Consultation ; Treatment Outcome

INTRODUCTIONMinimally invasive hepatectomy (MIH) for patients with hepatocellular carcinoma (HCC) is technically challenging, especially with large posteriorly located tumours or background of liver cirrhosis. This is a case-control study comparing the long-term oncological safety of HCC patients who underwent MIH and open hepatectomy (OH). Most of these patients have liver cirrhosis compared to other studies.

MATERIALS AND METHODSSixty patients were divided into 2 groups, 30 underwent MIH and 30 underwent OH for HCC resection. The patients in both groups were matched for extent of tumour resection, age and cirrhosis status. Patient characteristics, risk factors of HCC and all oncological data were studied.

RESULTSNegative resection margins were achieved in 97% of patients in both groups. The mean blood loss during surgery was significantly lower in the MIH group compared to the OH group (361 mL vs 740 mL; 95% CI, 222.2, 734.9; P = 0.04). Hospitalisation is significantly shorter in MIH group (7 days vs 11 days; 95% CI, 6.9, 12.2,; P = 0.04). Eight patients (27%) in the MIH group and 13 patients (43%) in the OH group developed HCC recurrence (P = 0.17). One, 3 and 5 years disease-free survival between MIH and OH groups are 76% vs 55%, 58% vs 47%, and 58% vs 39% respectively (P = 0.18). One, 3 and 5 years overall survival between MIH and OH groups are 93% vs 78%, 89% vs 70%, and 59% vs 65% respectively (P = 0.41).

CONCLUSIONMIH is a safe and feasible curative treatment option for HCC with similar oncological outcomes compared to OH. MIH can be safely performed to remove tumours larger than 5 cm, in cirrhotic liver, as well as centrally and posterior located tumours. In addition, MIH patients have significant shorter hospitalisation and intraoperative blood loss.

Blood Loss, Surgical ; Carcinoma, Hepatocellular ; complications ; pathology ; surgery ; Case-Control Studies ; Disease-Free Survival ; Hepatectomy ; methods ; Humans ; Laparoscopy ; Length of Stay ; Liver Cirrhosis ; complications ; Liver Neoplasms ; complications ; pathology ; surgery ; Margins of Excision ; Minimally Invasive Surgical Procedures ; methods ; Neoplasm Recurrence, Local ; epidemiology ; Tumor Burden

Recent studies suggest that liver cirrhosis is reversible after administering oral nucleos(t)ide analogue therapy to patients with hepatitis B virus (HBV) infection. However, few studies have addressed whether esophageal varices can regress after such therapy. We report a case of complete regression of esophageal varices during entecavir therapy in patients with HBV-related liver cirrhosis, suggesting that complications of liver cirrhosis such as esophageal varices can regress after the long-term suppression of HBV replication.
Abdomen/diagnostic imaging ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; Esophageal and Gastric Varices/complications/prevention & control ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*drug therapy/virology ; Humans ; Liver Cirrhosis/*diagnosis/etiology ; Male ; Middle Aged ; Polymerase Chain Reaction ; Ultrasonography

BACKGROUND/AIMS: Patients with liver cirrhosis (LC) are at risk for critical events leading to Intensive Care Unit (ICU) admission. Coagulopathy in cirrhotic patients is complex and can lead to bleeding as well as thrombosis. The aim of this study was to investigate bleeding complications in critically ill patients with LC admitted to a medical ICU (MICU). METHODS: All adult patients admitted to our MICU with a diagnosis of LC from January 2006 to December 2012 were retrospectively assessed. Patients with major bleeding at the time of MICU admission were excluded from the analysis. RESULTS: A total of 205 patients were included in the analysis. The median patient age was 62 years, and 69.3% of the patients were male. The most common reason for MICU admission was acute respiratory failure (45.4%), followed by sepsis (27.3%). Major bleeding occurred in 25 patients (12.2%). The gastrointestinal tract was the most common site of bleeding (64%), followed by the respiratory tract (20%). In a multivariate analysis, a low platelet count at MICU admission (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99) and sepsis (OR, 8.35; 95% CI, 1.04 to 67.05) were independent risk factors for major bleeding. The ICU fatality rate was significantly greater among patients with major bleeding (84.0% vs. 58.9%, respectively; p = 0.015). CONCLUSIONS: Major bleeding occurred in 12.2% of critically ill cirrhotic patients admitted to the MICU. A low platelet count at MICU admission and sepsis were associated with an increased risk of major bleeding during the MICU stay. Further study is needed to better understand hemostasis in critically ill patients with LC.
Aged ; Blood Platelets ; Critical Illness ; Female ; Gastrointestinal Hemorrhage/blood/diagnosis/*etiology/mortality ; Hospital Mortality ; Humans ; Intensive Care Units ; Liver Cirrhosis/blood/*complications/diagnosis/mortality ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Platelet Count ; Prognosis ; Republic of Korea ; Respiratory Tract Diseases/blood/diagnosis/*etiology/mortality ; Retrospective Studies ; Risk Factors ; Sepsis/blood/complications ; Time Factors

OBJECTIVETo compare the clinical features of children with different clinical forms of congenital hepatic fibrosis (CHF), and provides a description of the characteristics of childhood CHF.

METHODSSixty children with CHF between January 2002 and June 2015 were enrolled, including 26 children with portal hypertensive CHF (PH CHF), 3 children with cholangitic CHF, 30 children with combined portal hypertensive and cholangitic CHF (mixed CHF), and 1 child with latent forms of CHF. The medical data of 26 children with PH CHF and 30 children with mixed CHF, including gender, age, clinical manifestations, physical signs, laboratory tests and imaging characteristics, were retrospectively studied.

RESULTSFever, jaundice and hepatomegaly were more frequently noted in children with mixed CHF than in those with PH CHF (P<0.05). Splenomegaly and liver cirrhosis occurred more often in children with CHF, but there was no significant difference in the incidences of splenomegaly and liver cirrhosis between the children with PH CHF and mixed CHF. The plasma prothrombin activity, white blood cell counts, platelet counts, mean platelet volume, serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, γ-glutamyl transferase, leucine aminopeptidase, and total bile acids in children with mixed CHF were higher than in those with PH CHF (P<0.05). The decreased international normalized ratio and lower serum albumin levels were more frequently observed in children with mixed CHF than in those with PH CHF (P<0.05).

CONCLUSIONSPH and mixed CHF are common forms in childhood CHF. The children with the two forms of PH usually manifest portal hypertension such as cirrhosis and hepatosplenomegaly. The liver damage may be common in children with mixed CHF.

Adolescent ; Alkaline Phosphatase ; blood ; Child ; Female ; Genetic Diseases, Inborn ; complications ; diagnosis ; Humans ; Liver Cirrhosis ; complications ; diagnosis ; Male ; Splenomegaly ; etiology

BACKGROUND/AIMS: Levels of serum apelin (s-apelin), an endogenous ligand for angiotensin-like receptor 1, have been shown to be related to hepatic fibrosis and hemodynamic abnormalities in preclinical studies. We investigated the clinical implications of s-apelin as a noninvasive prognostic biomarker for chronic liver disease (CLD). METHODS: From January 2009 to December 2012, 215 CLD patients were enrolled and underwent clinical data collection, hepatic venous pressure gradient (HVPG) measurement, and liver biopsy. s-apelin was detected with a human total apelin enzyme-linked immunosorbent assay kit. All patients were prospectively observed during the median follow-up period of 23.0±12.9 months for decompensation and mortality. RESULTS: A total of 42 patients (19.5%) died during the follow-up period. s-apelin was significantly correlated with measurements of liver stiffness (R2=0.263, p<0.001) and collagen proportional area (R2=0.213, p<0.001) measured from liver biopsy tissue and HVPG (R2=0.356, p<0.001). In a multivariate analysis using a Cox regression hazard model, s-apelin was a weakly significant predictor of decompensation (hazard ratio [HR], 1.002; p<0.001) and mortality (HR, 1.003; p<0.001). CONCLUSIONS: s-apelin showed a significant relationship with CLD severity. However, its significance as a noninvasive biomarker for disease severity and prognosis was weak.
Adult ; Biomarkers/blood ; Biopsy ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Humans ; Hypertension, Portal/*blood/complications/mortality ; Intercellular Signaling Peptides and Proteins/*blood ; Liver/blood supply/pathology ; Liver Cirrhosis/*blood/etiology/mortality/pathology ; Male ; Middle Aged ; Portal Pressure ; Prognosis ; Proportional Hazards Models ; Prospective Studies

BACKGROUND/AIMS: This study aimed to clarify the effect of obesity on the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving antiviral treatment. METHODS: This study applied a retrospective analysis to a historical cohort in Bundang Jesaeng Hospital. In total, 102 CHB patients were treated with entecavir as an initial treatment for CHB and checked for obesity using a body composition analyzer. Hepatic steatosis was measured semiquantitatively using Hamaguchi’s scoring system in ultrasonography. Risk factors for the development of HCC were analyzed, including obesity-related factors (body mass index [BMI], waist circumference [WC], waist-to-hip ratio [WHR], visceral fat area [VFA], and hepatic steatosis). RESULTS: The median follow-up duration of the patients was 45.2 months (interquartile range: 36.0-58.3 months). The cumulative incidence rates of HCC at 1 year, 3 years, and 5 years were 0%, 5.3%, and 9.0%, respectively. Univariable analysis revealed that the risk factors for HCC development were a platelet count of <120,000 /mm² (hazard ratio [HR]=5.21, P=0.031), HBeAg negativity (HR=5.61, P=0.039), and liver cirrhosis (HR=10.26, P=0.031). Multivariable analysis showed that the significant risk factor for HCC development was liver cirrhosis (HR=9.07, P=0.042). However, none of the obesity-related risk factors were significantly associated with HCC: BMI ≥25 kg/m² (HR=0.90, P=0.894), WC ≥90 cm (HR=1.10, P=0.912), WHR ≥0.9 (HR=1.94, P=0.386), VFA ≥100 cm² (HR=1.69, P=0.495), and hepatic steatosis (HR=0.57, P=0.602). CONCLUSION: HCC development is associated with liver cirrhosis but not obesity-related factors in CHB patients receiving entecavir.
Adult ; Antiviral Agents/*therapeutic use ; Body Mass Index ; Carcinoma, Hepatocellular/epidemiology/*etiology ; Cohort Studies ; DNA, Viral/blood ; Female ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B virus/genetics/isolation & purification ; Hepatitis B, Chronic/complications/*drug therapy/virology ; Humans ; Incidence ; Liver Cirrhosis/complications ; Liver Neoplasms/epidemiology/*etiology ; Male ; Middle Aged ; Obesity/*complications ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Viral Load

PURPOSE: The present study aimed to investigate the role of hepatic venous pressure gradient (HVPG) for prediction of long-term mortality in patients with decompensated cirrhosis. MATERIALS AND METHODS: Clinical data from 97 non-critically-ill cirrhotic patients with HVPG measurements were retrospectively and consecutively collected between 2009 and 2012. Patients were classified according to clinical stages and presence of ascites. The prognostic accuracy of HVPG for death, survival curves, and hazard ratios were analyzed. RESULTS: During a median follow-up of 24 (interquartile range, 13-36) months, 22 patients (22.7%) died. The area under the receiver operating characteristics curves of HVPG for predicting 1-year, 2-year, and overall mortality were 0.801, 0.737, and 0.687, respectively (all p<0.01). The best cut-off value of HVPG for predicting long-term overall mortality in all patients was 17 mm Hg. The mortality rates at 1 and 2 years were 8.9% and 19.2%, respectively: 1.9% and 11.9% with HVPG < or =17 mm Hg and 16.2% and 29.4% with HVPG >17 mm Hg, respectively (p=0.015). In the ascites group, the mortality rates at 1 and 2 years were 3.9% and 17.6% with HVPG < or =17 mm Hg and 17.5% and 35.2% with HVPG >17 mm Hg, respectively (p=0.044). Regarding the risk factors for mortality, both HVPG and model for end-stage liver disease were positively related with long-term mortality in all patients. Particularly, for the patients with ascites, both prothrombin time and HVPG were independent risk factors for predicting poor outcomes. CONCLUSION: HVPG is useful for predicting the long-term mortality in patients with decompensated cirrhosis, especially in the presence of ascites.
Adult ; Aged ; Ascites/mortality ; Female ; Hepatic Veins/*physiopathology ; Humans ; Kaplan-Meier Estimate ; Liver Cirrhosis/blood/complications/diagnosis/*mortality/*physiopathology ; Liver Failure/diagnosis/*mortality/physiopathology ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; ROC Curve ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Venous Pressure